If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password
If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password
Corresponding author at: Outpatient Department of Cardiometabolic Medicine, Second Department of Cardiology, General Hospital Hippokration, Aristotle University of Thessaloniki, Greece.
Second Department of Internal Medicine, European Interbalkan Medical Center, Thessaloniki, GreeceOutpatient Department of Cardiometabolic Medicine, Second Department of Cardiology, General Hospital Hippokration, Aristotle University of Thessaloniki, Greece
Corticosteroids still represent one of the cornerstone treatment options for subjects hospitalized with coronavirus disease 2019 (COVID-19), especially for those suffering from a severe form of the disease [
]. Pulse methylprednisolone administered intravenously is a widely accepted treatment strategy for the induction of recession in subjects with acute flare or exacerbation of a background autoimmune disease, such as systemic lupus erythematosus, systemic vasculitis, or multiple sclerosis [
]. Based on the fact that COVID-19 is sometimes complicated by coagulopathy, vasculopathy, endothelial dysfunction and multisystem inflammatory response [
], pulse methylprednisolone appears a reasonable treatment option for the prevention of surrogate disease outcomes. A former meta-analysis of observational studies, also including a randomized controlled trial (RCT), by Mohanty and colleagues [
] failed to show any treatment benefit with pulse methylprednisolone versus standard corticosteroid dose for individuals hospitalized due to severe COVID-19.
Αn extensive literature search was performed in PubMed and Cochrane Library databases, searching for RCTs addressing the safety and efficacy of pulse methylprednisolone versus standard corticosteroid treatment dosage in patients with severe COVID-19, from inception to 16th January 2023. References of the eligible studies were also screened for potentially missed additional RCTs. No filter regarding sample size or publication language was imposed. Only RCTs enrolling adult subjects were included, while observational studies, case series and case reports were excluded. Narrative review articles and Editorials/commentaries were excluded, as well.
Risk for COVID-19 related death was predefined as the primary efficacy outcome. The risk for admission to intensive care unit (ICU) and the risk for initiation of ventilation with high-flow nasal cannula (HFNC) were set as secondary efficacy outcomes. The risk for secondary infections was assessed as the major safety endpoint of interest. As only dichotomous variables were assessed, differences were calculated with the use of risk ratios (RR), with 95% confidence interval (CI), after implementation of the Mantel-Haenszel (M-H) random effects formula. Statistical heterogeneity among studies was assessed by using I2 statistics. All analyses were performed at the 0.05 significance level, while they were undertaken with RevMan 5.3 software.
A total of 4 RCTs enrolling 559 subjects hospitalized due to severe COVID-19 were included in the final analysis [
MP3 pulses COVID-19 collaborative group Effect of intravenous pulses of methylprednisolone 250 mg versus dexamethasone 6 mg in hospitalised adults with severe COVID-19 pneumonia: an open-label randomised trial.
]. Details regarding pulse methylprednisolone regimen across the eligible RCTs is provided in supplementary Table 1.
Overall, pulse methylprednisolone did not have a significant effect compared to control on the risk for COVID-19 related death (RR = 0.83, 95% CI; 0.44-1.55, I2 = 7%), as shown in Fig. 1a. Restriction of our analysis to RCTs comparing pulse methylprednisolone to standard corticosteroid regimen (dexamethasone 6 mg once daily for up to 10 days) did not have a significant impact on the generated result (RR = 0.85, 95% CI; 0.47-1.54, I2 = 0%) [
MP3 pulses COVID-19 collaborative group Effect of intravenous pulses of methylprednisolone 250 mg versus dexamethasone 6 mg in hospitalised adults with severe COVID-19 pneumonia: an open-label randomised trial.
], whereas, when we compared the effect of pulse methylprednisolone versus no corticosteroid treatment, a significant effect was shown, based on data from the RCT conducted by Edalatifard et al. (RR = 0.14, 95% CI; 0.03-0.56, I2 not calculable) [
Concerning the secondary efficacy outcomes, treatment with pulse methylprednisolone versus control did not significantly affect the risk for admission to ICU (RR = 1.02, 95% CI; 0.46-2.27, I2 = 0%), as depicted in Fig. 1b, and the risk for initiation of HFNC (RR = 0.65, 95% CI; 0.26-1.63, I2 = 0%), as shown in Fig. 1c. Finally, regarding the major safety endpoint of interest, pulse methylprednisolone treatment did not have a significant impact on the risk for secondary infections among subjects hospitalized due to severe COVID-19 (RR = 0.51, 95% CI; 0.16-1.61, I2=64%), as shown in Fig. 1d.
To sum up, pulse methylprednisolone was not shown to be superior to standard corticosteroid dosages, whereas it is probably superior to no corticosteroid treatment in cases of severe COVID-19. In addition, pulse methylprednisolone treatment does not increase the risk for secondary infections, which can complicate disease course of COVID-19 patients. Therefore, pulse methylprednisolone treatment in severe COVID-19 should not be recommended; however, it has to be determined in focused and well-designed RCTs whether it is superior to standard corticosteroid dosing regimens in specific patients’ subgroups, such as those developing multisystem inflammatory syndrome or acute respiratory distress syndrome.
Effect of intravenous pulses of methylprednisolone 250 mg versus dexamethasone 6 mg in hospitalised adults with severe COVID-19 pneumonia: an open-label randomised trial.
00048-1&id=gr1.jpg){kind=link}